Identifying the Most Important Factors in Determining the Osteoporosis in Women Using Data Mining Techniques

Osteoporosis is one of the primary causes of disability and mortality in the elderly. If osteoporosis's significant features can be identified, the risk of developing this disease will be reduced. In recent years, data mining approaches have become a suitable tool for medical researchers. This study applied data mining methods to identify osteoporosis’s significant features. This study applied data from women having osteoporosis or osteopenia in the period 2011-2019 in the Osteoporosis Diagnosis Center, Isfahan, Iran. Data mining methods such as linear regression, naïve bayes, decision tree, support vector machine, random forest, and neural network were implemented on the dataset. This study consisted of 8258 patients’ information, of which 1482 had osteoporosis. The results showed that the support vector machine, decision tree, neural network are the best method based on accuracy, precision, and AUC measures. Six candidate features were age, weight, back pain, low activity, menopause date, and previous fracture. Support vector machine, decision tree, and neural network are the best candidate techniques for predicting osteoporosis. Thin older people are more at risk of osteoporosis than other people. Yet, people with middleweight and middle age are at lower risk of osteoporosis

PHARMACOGENOMICS IN THE EMIRATI POPULATION: APPLICATIONS IN CARDIOVASCULAR DISEASES AND ONCOLOGY

Pharmacogenetic variations contribute to interindividual differences in drug response. Advances in molecular techniques provided insights into interpopulation pharmacogenomic variations. A limited number of pharmacogenetic studies were conducted in the UAE population. The current study aims to explore the variation landscape in important pharmacogenes in Emiratis. Furthermore, it investigates the association between VKORC1 variants and warfarin dose in cardiovascular patients. Finally, this study explores the applied/needed germline pharmacogenetic tests in oncology in the UAE. In 100 healthy Emiratis, variants and star alleles in 100 relevant pharmacogenes were defined by next-generation sequencing. 63% of detected variants were rare, 30% were novel, and 141 variants were novel and damaging. By clinical annotations, filtering variants resulted in 99 clinically actionable variants, from which 44 are highly significant alleles. Revising the results against the clinical pharmacogenetics implementation consortium guidelines demonstrated that 93% of participants have at least one actionable variant with a dosing recommendation. The effect of VKORC1 on warfarin dose was explored in 90 patients. A model built from two VKORC1 variants, rs9923231 and rs61742245, with age, significantly predicted warfarin dose. High incidence rates of adverse chemotherapy effects were reported from 66 pediatric acute lymphoblastic leukemia patients, which indicates the plausibility of pharmacogenetic research to investigate toxicity biomarkers. Few cases had a clinical pharmacogenetic test of TPMT and NUDT15 before starting oral 6-mercaptopurine. Patients who received pharmacogenetic-guided doses suffered from less adverse effects. Exploring the adverse drug effects in a group of 77 breast cancer patients was faced by deficiencies in adverse effects reporting. The reported adverse events suggested suitable candidates for future pharmacogenetic research. This research highlighted population-specific variants, unexplored adverse drug events, and possible pharmacogenomics applications in the UAE. Various research opportunities were illustrated for the scientific community

Safety Assessment of Medications in Elderly: Contribution of the Pharmacovigilance System

As a result of the industrialisation and technological and scientific advances in healthcare, there has been a substantial increase in aging of the population worldwide, and Portugal is no exception. In fact, in Portugal, the average life expectancy is increasing and therefore the number of elderly people. Additionally, the proportion of elderly patients with multiple comorbidities is rising, which in turn leads to an increase in medication use and in the risk of adverse drug reactions (ADRs). In fact, ADRs in elderly can be considered a public health problem, having high costs and being a relevant cause of hospitalization and mortality. Pharmacovigilance is the science concerned with the detection, analysis, evaluation, understanding, and prevention of ADRs. It is a fundamental area for the continuous monitoring of the safety of medicines, particularly relevant in the initial periods of the widespread marketing of new drugs, due to relative scarcity of drug safety information available at the time of marketing authorization, which arises, at this stage, essentially based on pre-marketing clinical trials. Pharmacovigilance allows the identification of problems related to the use of drugs, which are often detected in the post-marketing phase. This is essential to prevent and minimize potential iatrogenic risks to the health of patients. Therefore, monitoring the iatrogenicity of medication that particularly affects elderly patients is fundamental to maximize the safety information of medicines in this special population. Additionally, there is an increasing prevalence of elderly patients with diabetes mellitus and musculoskeletal diseases, whereby is important the knowledge generated from real-world pharmacovigilance data to minimize the risk of harm that may occur with drugs used for the treatment of these conditions. The central aim of this work was to characterize the ADRs profile in elderly patients spontaneously reported to the Portuguese Pharmacovigilance System (PPS). Additionally, this work also intended to characterize the ADRs in elderly diabetic patients and to evaluate the safety of non-steroidal anti-inflammatory drugs (NSAIDs) in this age group. For this propose, firstly, all spontaneous ADRs reported to the PPS from 2013 to 2017 were examined. However, considering the aim of this study, ADRs referring to patients aged 65 and over were analysed in higher detail and compared with those reported in non-elderly adults. Secondly, a retrospective analysis of suspected ADRs reports from PPS between 2008 to 2018 was performed, involving patients aged ≥65 years with diabetes mellitus. Finally, it was carried out a comprehensive literature review of NSAIDs safety in elderly patients and, in parallel, considering the same period of time (i.e., 2008-2018), the suspected ADRs related to these drugs reported to a database of pharmacovigilance, for people aged ≥65, were analysed. Reports were analysed in terms of gender of the involved patients, seriousness and type of ADRs, according to the “System Organ Class” from the Medical Dictionary for Regulatory Activities terminology. In the reports with fatal outcome a deeper analysis in terms of “Preferred Term” for each report was performed. In the general analysis of spontaneous reports in the elderly, the most frequent suspected ADRs fall within the categories of general disorders and administration site conditions, and skin and subcutaneous tissue complaints. Regarding the therapeutic agents involved, the antineoplastic drugs were the most commonly implicated. In addition, the antineoplastic and antithrombotic drugs were the most represented pharmacotherapeutic groups of suspected drugs involved in patient’s death. In the analyses of ADRs in elderly diabetic patients, the most frequent were hypoglycaemia and lactic acidosis, and the drugs specifically indicated for glycaemic control were the most frequently involved. Finally, in the literature review performed on NSAIDs safety in elderly patients, most studies concluded that the risk of a gastrointestinal adverse event with the use of cyclooxygenase-2 (COX-2)-selective NSAIDs seems to be lower when compared with conventional NSAIDs. In addition, celecoxib was considered the safest of all other NSAIDs. However, the risk of gastrointestinal events in patients aged ≥75 years taking selective COX-2 inhibitors was higher when compared with younger patients. Additionally, diclofenac was associated with relevant renal adverse events in patients aged 75 years or older as well as in those with some renal impairment. Regarding cardiovascular events the incidence was lower with coxibs than with conventional NSAIDs and celecoxib led to a lower incidence of these events when compared with etoricoxib. In the analysis performed in PPS data most of suspected ADRs had diclofenac as suspected drug. The suspected ADRs most frequently reported fall within the categories of skin and subcutaneous tissue disorders. Serious gastrointestinal ADRs occurred mostly in patients taking more than one NSAID and/or another concomitant drug that increases the incidence of these events, in the absence of gastroprotection. The majority of serious ADRs related to renal and cardiac disorders occurred in patients with history of renal disorders or diabetes mellitus and hypertension, respectively. All the studies performed with the data belonging to PPS concluded that the majority of ADRs were serious, occurred predominantly in female and were expected. Hence, an accurate identification of ADRs, especially the detection of preventable ADRs, is an important starting point to improve drug safety in elderly. Therefore, studies targeting elderly patients are needed to improve the safety information of these drugs in this special population, considering their multiple medical conditions, thus highlighting the importance of active pharmacovigilance. In this context, it is important to emphasize that pharmacovigilance databases are important tools to evaluate issues related to the safety of drugs in older people, enabling to improve the knowledge on the safety profile of medicines in these patients.Com a industrialização e os avanços tecnológicos e científicos na área da saúde, tem-se assistido a um aumento substancial do envelhecimento da população a nível mundial, e Portugal não é exceção. De facto, em Portugal, a esperança média de vida está a aumentar e, consequentemente, o número de idosos. Além disso, a proporção de doentes idosos com múltiplas comorbilidades está a aumentar, o que, por sua vez, leva a um aumento no uso de medicamentos e a um acréscimo do risco de reações adversas a medicamentos (RAMs). Na verdade, as RAMs em idosos podem ser consideradas um problema de saúde pública, com custos elevados, pois são uma causa relevante de hospitalização e mortalidade. A farmacovigilância é a ciência que se centra na deteção, análise, avaliação, compreensão e prevenção de RAMs. É uma área fundamental para a monitorização contínua da segurança dos medicamentos, especialmente relevante nos períodos iniciais da comercialização alargada de novos fármacos, devido à escassez relativa de informação de segurança disponível no momento da autorização de introdução no mercado, a qual advém, nesta fase, essencialmente dos ensaios clínicos conduzidos durante a fase de pré-comercialização. A farmacovigilância permite a identificação de problemas relacionados com o uso de medicamentos, frequentemente detetados apenas na fase de pós-comercialização. Isso é essencial para prevenir e minimizar os riscos iatrogénicos potenciais para a saúde dos doentes. Portanto, monitorizar a iatrogenicidade dos medicamentos, a qual afeta de uma forma mais marcada os doentes idosos, é fundamental para maximizar a informação de segurança dos mesmos nesta população especial. Além disso, há uma prevalência crescente de doentes idosos com quadros clínicos de multipatologia, incluindo a presença de diabetes mellitus e doenças músculo-esqueléticas, sendo importante o conhecimento gerado a partir dos dados de farmacovigilância obtidos em contexto de vida real para minimizar os riscos decorrentes do uso de medicamentos nestas condições. O objetivo central deste trabalho consistiu na caraterização do perfil de RAMs em doentes idosos, em Portugal, notificadas espontaneamente ao Sistema Nacional de Farmacovigilância (SNF). Adicionalmente, esta tese contemplou também a caracterização das RAMs em doentes idosos diabéticos e a avaliação da segurança dos fármacos anti-inflamatórios não esteroides (AINEs) nesta faixa etária. Para tal, em primeiro lugar, foram avaliadas todas as RAMs comunicadas ao SNF de 2013 a 2017. No entanto, considerando o objetivo deste estudo, as RAMs referentes a doentes com 65 ou mais anos foram analisadas detalhadamente e comparadas com as que foram notificadas em adultos não idosos. Em segundo lugar, foi realizada uma análise retrospetiva das notificações de suspeitas de RAMs submetidas ao SNF entre 2008 e 2018, envolvendo doentes com idade ≥65 anos com diabetes mellitus. Por fim, foi realizada uma revisão compreensiva da literatura sobre a segurança dos AINEs em doentes idosos e, em paralelo, considerando o mesmo período de tempo (i.e., 2008-2018) foram analisadas as suspeitas de RAMs relacionadas com este tipo de medicamentos, manifestadas em indivíduos com 65 ou mais anos e notificadas para o SNF. As notificações foram analisadas relativamente ao género dos doentes envolvidos, gravidade e tipo de RAMs, de acordo com a terminologia “Classe de Sistemas e Órgãos” do dicionário médico para a atividade regulamentar. Nos casos com desfecho fatal, foi realizada uma análise mais aprofundada em termos do “Termo Preferencial” para cada caso. Na análise geral das notificações espontâneas em idosos, as RAMs mais frequentes enquadraram-se nas categorias de distúrbios gerais e perturbações no local de administração e afeções da pele e do tecido subcutâneo. Em relação aos grupos terapêuticos envolvidos, os medicamentos antineoplásicos foram os mais comumente implicados. Além disso, os medicamentos antineoplásicos e antitrombóticos foram os grupos farmacoterapêuticos mais representados entre os medicamentos suspeitos envolvidos na morte de doentes. Mediante análise das RAMs em doentes idosos diabéticos, as mais frequentes foram a hipoglicémia e a acidose láctica, sendo os medicamentos especificamente indicados para o controlo glicémia os mais frequentemente envolvidos. Finalmente, tendo em conta a revisão da literatura realizada referente à segurança de AINEs em doentes idosos, a maioria dos estudos concluiu que o risco de um evento adverso gastrointestinal é inferior com o uso de AINEs seletivos para a isoenzima cicloxigenase-2 (COX-2) do que com o uso de AINEs convencionais. Mais especificamente, entre os AINEs, o celecoxib foi considerado o fármaco mais seguro. No entanto, o risco de eventos gastrointestinais em doentes com idade ≥75 anos a tomar AINEs seletivos para COX-2 foi maior que o observado em doentes mais jovens. Além disso, o diclofenac foi associado a eventos adversos renais relevantes em doentes com 75 ou mais anos, bem como naqueles com algum grau de insuficiência renal. Em relação aos eventos adversos cardiovasculares, a sua incidência foi menor com os coxibes do que com os AINEs convencionais, e o celecoxib levou a uma incidência menor desses eventos quando comparado ao etoricoxib. Em resultado da análise realizada aos dados do SNF, foi possível constatar que a maioria das suspeitas de RAMs envolveu o diclofenac. As suspeitas de RAMs mais frequentemente relatadas enquadraram-se nas categorias de afeções da pele e do tecido subcutâneo. As RAMs gastrointestinais graves ocorreram principalmente em doentes a tomar mais que um AINE e/ou outro medicamento concomitante, o que aumenta a incidência desses eventos, na ausência de gastroproteção. A maioria das RAMs graves relacionadas com distúrbios renais ou distúrbios cardíacos ocorreram em doentes com história clínica de distúrbios renais ou diabetes mellitus e de hipertensão arterial, respetivamente. Todos os estudos realizados com os dados do SNF que suportam esta tese concluíram que a maioria das RAMs eram graves, ocorreram predominantemente em mulheres e eram expetáveis. A identificação exata de RAMs, especialmente a deteção de RAMs evitáveis, é um ponto de partida importante para melhorar a segurança dos medicamentos em idosos. Portanto, estudos direcionados para a população geriátrica são necessários para melhorar a informação de segurança desses medicamentos nesta população especial, considerando as suas múltiplas condições médicas, destacando-se assim a importância da farmacovigilância ativa. Nesse contexto, é importante enfatizar que as bases de dados de farmacovigilância são ferramentas importantes para avaliar questões relacionadas com a segurança dos medicamentos em idosos, possibilitando aprimorar o conhecimento sobre o perfil de segurança de medicamentos nestes doentes

The change of lifestyle in an indigenous Namibian population group (Ovahimba) is associated with alterations of glucose metabolism, metabolic parameters, cortisol homeostasis and parameters of bone ultrasound (quantitative ultrasound).

Die Anzahl der an Diabetes mellitus Erkrankten hat in den letzten Jahren weltweit rapide zugenommen, und es wird erwartet, dass die Zahlen weiterhin ansteigen: von 171 Millionen im Jahr 2000, 382 Millionen im Jahr 2013 und auf 592 Millionen Diabetes-Kranker im Jahr 2030 (Hossain et al. 2007). Früher wurde der Diabetes mellitus, besonders Diabetes mellitus Typ 2 (DM) als eine Krankheit der reichen und damit der westlichen industrialisierten Länder gesehen (King et al. 1991). Dieses Bild hat sich gewandelt, da mehr und mehr Daten aus Entwicklungsländern vorliegen, die einen beängstigenden Anstieg der Prävalenz des Diabetes mellitus zeigen. Aus diesen Gründen widmete sich unsere Studie primär der Frage, inwiefern sich für eine spezifische indigene namibische Bevölkerungsgruppe (Ovahimba) darstellen lässt, dass die Veränderung der Lebensweise im Rahmen der Urbanisierung mit einer erhöhten Prävalenz von Glukosestoffwechselstörungen einhergeht. Sekundär wurde der Cortisolhaushalt der Probanden mit der Fragestellung untersucht, ob ein erhöhter psychosozialer Stress, welcher häufig mit dem Prozess der Urbanisierung assoziiert ist, mit erhöhten Cortisolwerten in unserer Studienkohorte einhergeht. Weiterhin wurden die Facetten des Metabolischen Syndroms (MetS) untersucht und der Framingham risk score (FRS) berechnet um das kardiometabolische Risikoprofil der Studienkohorte zu beurteilen. Ferner wurde die Knochengesundheit osteosonometrisch mit der Fragestellung untersucht, ob die Änderung des Lebensstils im Rahmen der Urbanisierung einen Einfluss auf die Knochendichte hat. Da unsere Studie die erste Studie in dieser Form bei den Ovahimba war, galt es auch, Grunddaten für mögliche weiterführende Studien zu erlangen. In diesem Kontext untersuchten wir zwei Studiengruppen: Gruppe 1, auch als ‚städtische Gruppe‘ bezeichnet, bestand aus sechzig Probanden, die seit mindestens drei Jahren in der Stadt Opuwo leben und so dem Prozess der Urbanisierung ausgesetzt sind. Gruppe 2, auch als ‚ländliche‘ Gruppe bezeichnet, setzte sich aus 63 Probanden zusammen, die in den ländlichen Gebieten des Kaokovelds im Nord-Westen Namibias, einer traditionellen Lebensweise nachgehen. Die anthropometrischen Daten der Probanden wurden erhoben und mit den Probanden der orale Glukose Toleranz Test (OGTT) durchgeführt. Weiterhin wurde mittels Body Impedance Analysis (BIA) die Körperzusammensetzung analysiert und ferner die Fettstoffwechselparameter untersucht um kardiometabolische Risikofaktoren zu identifizieren und die Prävalenz des Metabolischen Syndroms als auch den FRS berechnen zu können. Außerdem wurde zu Sonnenaufgang und Sonnenuntergang jeweils eine Speichelprobe für die Analyse des Cortisolhaushalts entnommen. Die Knochendichte wurde mittels quantitativen Ultraschalls ermittelt. In dem ersten Schritt der statistischen Analyse wurde eine deskriptive Analyse der Daten mittels des Exakten Fishers Tests und eines zweiseitigen t-Tests durchgeführt. Das Signifikanz Niveau wurde bei 5% festgelegt. In einem zweiten Schritt der statistischen Analyse wurden die Daten für verschiedene Störfaktoren adjustiert. Weiterhin wurde ein möglicher Zusammenhang zwischen Glukosestoffwechselstörung, MetS und Cortisolhaushalt mittels des Mann-Whitney-U Tests untersucht. In einem dritten Schritt der statistischen Analyse wurde der Pearson’s Korrelationskoeffizient zwischen Area under the Line (AUL) des Cortisols und den metabolischen Parametern als auch den Knochendichtemessungen errechnet. Die Analyse zeigte statistisch signifikante Unterschiede in allen anthropometrischen Daten (Alter, Größe, Gewicht, Taillen- und Hüftumfang, BMI, systolisch und diastolischer Blutdruck vor körperlicher Betätigung und systolischer Blutdruck und Puls nach körperlicher Betätigung) außer Geschlecht, diastolischer Blutdruck nach körperlicher Betätigung und Puls in Ruhe. Die Daten des Glukosestoffwechsels zeigten signifikante Unterschiede in der Nüchternglukose und dem 2-Stunden Glukosewert, aber nicht im HbA1c Wert. Die Analyse der primären Fragestellung ‚Glukosestoffwechselstörung: ja/nein‘ zeigte signifikante Unterschiede zwischen der ländlichen und der städtischen Gruppe (Gruppe 1 28.3% vs. Gruppe 2 12.7%). Allerdings zeigten sich keine signifikanten Unterschiede in den einzelnen Komponenten der Glukosestoffwechselstörung (Diabetes mellitus Typ 2 3.35 vs. 0.0%, gestörte Glukosetoleranz 18.3% vs. 7.9%, gestörte Nüchternglukose 6.7% vs. 4.8%). Die Untersuchung des Fettstoffwechsels und der Körperzusammensetzung zeigte signifikante Unterschiede der Triglyzerid, HDL-Chol, LDL-Chol (vor Adjustierung) Konzentration und die Körpermasse nach Adjustierung. Ein signifikanter Unterschied zeigte sich im Mittelwert der Cortisol Konzentration bei Sonnenaufgang und –untergang, der absoluten Cortisol Abnahme und der AUL. Die Prävalenz des Metabolischen Syndroms war signifikant höher in Gruppe 1 im Vergleich zu Gruppe 2 (Gruppe 1 31.7% vs. Gruppe 2 7.9%). Die Berechnung des Framingham risk scores ergab folgende Werte: Gruppe 1 hat ein 10-Jahre kardiovaskuläres Risiko von 5.3 ± 5.3% und Gruppe 2 von 5.5 ± 7.9%, der Unterschied war nicht signifikant. Die Analyse der Knochendichte ergab nur zwei signifikante Unterschiede zwischen den Studiengruppen: die SOS Daten nach Adjustierung für ‚Geschlecht‘, ‚Alter‘ und ‚Größe‘ und die SOS und SI Daten nach Adjustierung für ‚Geschlecht‘, ‚Alter‘, ‚Größe‘ und ‚Gewicht‘. Der Mittelwert des Z-Wertes lag bei +1.6 ± 1.6. Die Ergebnisse unserer Studien zeigen, dass die Veränderung der Lebensweise der Ovahimba im Rahmen der Urbanisierung bereits unerwünschte gesundheitliche Folgen mit sich bringt. Der signifikante Unterschied in der Prävalenz der Glukosestoffwechselstörung zwischen der städtischen und der ländlichen Kohorte unterstützt unsere Hypothese, dass eine Veränderung der Lebensweise mit einem erhöhten Risiko für Glukosestoffwechselstörungen assoziiert ist. Durchgeführte Studien haben gezeigt, dass es im Rahmen der Urbanisierung häufig zu erhöhtem psychosozialem Stress kommt und damit zu erhöhten Cortisolkonzentrationen. Die Hypothese, dass die städtischen Probanden höhere Cortisolwerte und eine höhere Cortisol AUL auf Grund der Urbanisierung aufweisen, konnte verifiziert werden. Weitere ungewünschte Aspekte der Urbanisierung sind das hohe Auftreten von metabolischen und kardiovaskulären Risikofaktoren. Unsere Studienkohorte zeigte eine Gesamt-Prävalenz des MetS von 19.5% mit einem signifikanten Unterschied zwischen den einzelnen Gruppen (Gruppe 1 31.7% vs. Gruppe 2 7.9%). Die Berechnung des FRS ergab folgende Werte: 48.0% niedriges Risiko, 43.9% mittleres Risiko, 5.7% hohes Risiko und 1.6% sehr hohes Risiko in den nächsten 10 Jahren eine kardiovaskuläre Krankheit zu erleiden. Der Unterschied zwischen den zwei Studiengruppen war nicht signifikant. Die Knochendichtemessungen wurden durchgeführt um Rohdaten für weitere Studien zu erlangen und um mögliche Auswirkungen der Urbanisierung zu untersuchen. Unsere Hypothese, dass die städtischen Probanden eine schlechtere Knochendichte aufweisen, konnte partiell bestätigt werden. Zwei Parameter ergaben einen statistisch signifikanten Unterschied: erstens der SOS-Wert nach Adjustierung für ‚Geschlecht‘, ‚Alter‘ und ‚Größe‘ und der SOS und SI-Wert nach Adjustierung für ‚Geschlecht‘, ‚Alter‘, ‚Größe‘ und ‚Gewicht‘ (SOS: ps+a+h = 0.004, ps+a+h+w < 0.001; SI: ps+a+h+w = 0.025). Diese signifikanten Unterschiede nach Adjustierung könnten ein erster Hinweis für eine negative Beeinflussung der Knochendichte der Ovahimba nach Veränderung ihrer Lebensweise sein. Der Mittelwert des SI - Z-Werts der Gesamtkohorte lag bei +1.6 ± 1.6 Standard Deviationen über dem Wert einer gleichaltrigen gesunden Person der gleichen Ethnizität. Dies zeigt, dass die Ovahimba eine bessere Knochendichte als Afro-Amerikaner aufweisen. Zusammenfassend hat unsere Studie gezeigt, dass Urbanisierung mit einem erhöhten Risiko für Glukosestoffwechselstörung in den Ovahimba assoziiert ist. Weiterhin konnten wir zeigen, dass Urbanisierung mit erhöhten Cortisolwerten, einer Veränderung der Knochendichte und der metabolischen Parameter einschließlich des Metabolischen Syndroms, einhergeht.The number of patients suffering from diabetes mellitus type 2 (DM) worldwide has increased rapidly over the past few years and it is expected that the numbers will increase further: from 171 million people suffering from diabetes in 2000, to 382 million in 2013 and to 592 million people by 2035 (IDF 2013, Hossain et al. 2007). Until some time ago diabetes, especially type 2 DM, was seen as a disease of the more affluent and therefore of the western industrialised world (King & Rewers 1991). However, this picture is changing as more and more data from the developing world become available showing an alarming rise of the prevalence of DM in these countries. Therefore, the aim of our study was to assess the association of lifestyle changes and modification of the social environment in the face of urbanisation on the risk for a disorder of glucose metabolism in the Ovahimba people of Namibia. Secondary to this, the cortisol homeostasis of the participants was investigated with the question whether urban compared to rural participants have a higher cortisol exposure due to increased psychosocial stress. In order to assess the cardio-metabolic risk profile of the Ovahimba, the prevalence of the metabolic syndrome (MetS) was ascertained and the participants’ 10-year cardiovascular risk was calculated according to the Framingham risk score (FRS). Lastly, the acoustical properties of bone of the study cohort were examined with the question whether lifestyle changes affect bone quality. No study with the above-mentioned questions has been conducted in the Ovahimba yet; therefore another aim of our study was to establish baseline data for further research. In order to answer the above questions, two groups of participants were formed from the Ovahimba community in Namibia: ‘Group 1’, also called ‘urban group’ consisted of participants having been living in the town of Opuwo for at least three years, thus being subjected to urbanisation and ‘westernisation’. ‘Group 2’, also called ‘rural group’ consisted of participants living a traditional lifestyle in the rural area of the Kaokoveld in north-western Namibia. Each participant underwent the oral glucose tolerance test. In addition, anthropometric measurements were taken, the body fat and lean mass measured by body impedance analysis (BIA) and the fat metabolism examined to identify cardiovascular risk factors, assess the prevalence of the MetS and calculate the 10-year cardiovascular risk. In addition, two saliva samples were collected, one at sunrise and one at sunset to examine the cortisol homeostasis and a possible association with dysglycaemia, the MetS and low quality of bone. Lastly, bone ultrasound was used to determine the acoustical properties of bone of the participants. In the first step of statistical analysis a descriptive analysis of the data was performed as a group comparison. Nominal variables were evaluated using Fisher’s exact test. A two-sided t-test was applied to the continuous variables with the null-hypothesis of equal mean values in both groups. A prevalence of 5% was taken as the basis for the statistical power. In a second step of statistical analysis, the data were adjusted for various confounders. In addition, a Mann-Whitney-U test was applied to the data of disorder of glucose metabolism, MetS and cortisol concentration to assess a possible association of cortisol concentration and the presence or not of dysglycaemia and MetS. In a third step of statistical analysis, the Pearson’s correlation was calculated for the cortisol area under the line (AUL) and metabolic parameters as well as bone ultrasound measurements. The analysis showed significant differences in all anthropometrical data (age, height, weight, hip and waist circumference (WC), body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP) before and after exercise and heart rate after exercise) except for ‘sex’, ‘diastolic BP after exercise’ and ‘heart rate at rest’. The characteristics of glucose metabolism showed significant differences of the fasting glucose (FG) and 2-hours glucose, but not of the HbA1c. The analysis of the primary question ‘disorder of glucose metabolism: yes/no’ presented a significant difference between the urban and the rural group (Group 1 28.3% vs. Group 2 12.7%), but this significance was not present in the individual components (diabetes mellitus type 2 (DM) 3.3% vs. 0.0%, impaired glucose tolerance (IGT) 18.3% vs. 7.9%, impaired fasting glucose (IFG) 6.7% vs. 4.8%). The investigation of the fat metabolism and BIA measurements showed significant differences for triglycerides, HDL-Chol, LDL-Chol before adjustment and lean body mass after adjustment. A significant difference was seen in the mean saliva cortisol concentrations at sunrise and sunset, the mean absolute decline of cortisol concentration and the cortisol AUL. The relative decline was not significantly different. The prevalence of the MetS was significantly higher in the urban group (Group 1 31.7% vs. Group 2 7.9%). Looking at the Framingham risk score, Group 1 showed a 10-year cardiovascular risk of 5.3 ± 5.3% and Group 2 of 5.5 ± 7.9%, with no significant difference. The analysis of the bone ultrasound measurements only showed two significant differences between the urban and the rural group: the SOS data after adjustment for ‘sex’, ‘age’ and ‘height’ and the SOS and SI data after adjustment for ‘sex’, ‘age’, ‘height’ and ‘weight’. The mean Z-score of the study cohort was +1.6 ± 1.6 standard deviations. There was only a weak correlation between milk consumption and walking time and bone ultrasound measurements. The interpretation of the results of our study showed that the Ovahimba of Namibia are not spared the adverse effects of urbanisation and westernisation. The significant difference in the presence of a disorder of glucose metabolism between the urban and rural group supports the hypothesis that urbanisation concurrent with a change of lifestyle was associated with an increased risk of dysglycaemia in our study cohort. Research has shown that psychosocial stress, a condition often associated with urbanisation leads to an alteration of the cortisol homeostasis with increased cortisol exposure. The urban participants had significantly higher mean concentrations at sunrise and sunset and a higher cortisol AUL, supporting our hypothesis that urban participants will present higher cortisol exposure due to increased psychosocial stress. Another adverse effect of urbanisation is the high prevalence of metabolic and cardiovascular disorders. Our study population presented a prevalence of the MetS of 31.7% in the urban and 7.9% in the rural group, showing a significant difference. The calculation of the FRS showed that of the total study cohort, 48.0% were at low risk, 43.9% at moderate risk, 5.7% at high risk and 1.6% at very high risk of incurring a cardiovascular event in the next 10 years. This assessment tool showed no significant difference between the two study groups. The acoustical properties of bone were measured to establish baseline data for future studies and to assess the impact of urbanisation on bone quality. Our hypothesis that urban participants will have a lesser bone quality could partially be verified. There were two measurements of bone ultrasound that showed a statistically significant difference between the urban and the rural group. Firstly, the SOS measurement after adjustment for ‘sex’, ‘age’ and ‘height’ and ‘sex’, ‘age’, ‘height’ and ‘weight’ (ps+a+h = 0.004, ps+a+h+w < 0.001); and secondly the SI measurement after adjustment for ‘sex’, ‘age’, ‘height’ and ‘weight’ (ps+a+h+w = 0.025). This significant difference in the SOS and SI measurement after adjustment could be the first indication that a change of lifestyle affects bone ultrasound measurements in the Ovahimba. The mean SI - Z-score of the whole cohort was 1.6 standard deviations above that for a person of the same age, gender and ethnicity. This indicates that the Ovahimba have greater bone strength compared to the Afro-Americans. In conclusion, our study has shown that urbanisation is associated with an increased risk for a disorder of glucose metabolism in Ovahimba people. We could furthermore show that urbanisation is associated with an increased cortisol exposure, alterations of metabolic parameters including the metabolic syndrome and parameters of bone quality.

Skills in Rheumatology

This Open Access book presents practical approaches to managing patients affected by various rheumatological diseases, allowing readers to gain a better understanding of the various clinical expressions and problems experienced by these patients. Discussing rheumatology from an organ systems perspective, it highlights the importance ofdetailed musculoskeletal examinations when treating patients affected by rheumatological diseases. The book first explores the latest diagnostic approaches and offers key tips for accurate musculoskeletal examinations before addressing the various treatment modalities, with a particular focus on the most common joints involved in rheumatoid arthritis: the wrists and the metacarpophalangeal joints (2nd and 3rd). Featuring easy-to-understand flow diagrams and explaining the common medical problems associated with rheumatic disease, such as shortness of breath and anemia, it is not only a valuable resource to rheumatologists, but will also appeal to medical students, junior residents, and primary healthcare physicians